1. Field of the Invention
The present invention relates to a time-of-flight mass spectrometer and method of time-of-flight mass spectrometry used in quantitative analysis and simultaneous qualitative analysis of trace compounds and also in structural analysis of sample ions.
2. Description of Related Art
A time-of-flight (TOF) mass spectrometer is an instrument that finds the mass-to-charge ratio (m/z) of each ion by accelerating ions with a given accelerating voltage Va, causing them to fly, and calculating the m/z from the time taken for each ion to reach a detector. At this time, from the law of conservation of energy, the following Eq. (1) holds.
                                          mv            2                    2                =                  zeV          a                                    (        1        )            where v is the velocity of the ion, m is the mass of the ion, z is the valence number of the ion, and e is the elementary charge.
From Eq. (1), the velocity v of the ion is given by
                    v        =                                            2              ⁢                                                          ⁢                              zeV                a                                      m                                              (        2        )            
Therefore, the flight time T required for the ion to reach a detector, placed behind at a given distance of L, is given by
                    T        =                              L            v                    =                      L            ⁢                                          m                                  2                  ⁢                                                                          ⁢                                      zeV                    a                                                                                                          (        3        )            
As can be seen from Eq. (3), ions can be separated according to m/z value by employing the fact that the flight time T differs according to m/z of each ion.
The results obtained by TOF mass spectrometry give a relationship between m/z values converted from the flight time T and the ion intensity at each m/z value. A spectrum in which this relation is represented is known as a mass spectrum. At this time, the work to convert the flight time T into m/z is known as calibration. A formula used for the conversion is known as a calibration formula. Theoretically, the conversion can be made using Eq. (3). In order to obtain higher mass accuracy, polynomial expressions for absorbing systematic errors are often used.
A linear TOF mass spectrometer in which ions are made to fly linearly from an ion source to a detector as shown in FIG. 16A and a reflectron TOF mass spectrometer in which a reflectron field is placed between an ion source and a detector to improve energy focusing and to prolong the flight distance as shown in FIG. 16B have enjoyed wide acceptance.
The mass resolution R of a TOF mass spectrometer is defined as follows:
                    R        =                  T                      2            ⁢                                                  ⁢            Δ            ⁢                                                  ⁢            T                                              (        4        )            where T is the total flight time and ΔT is a peak width.
That is, if the peak width ΔT is made constant and the total flight time T can be lengthened, the mass resolution can be improved. However, in the related art linear or reflectron type TOFMS, increasing the total flight time T (i.e., increasing the total flight distance) will lead directly to an increase in instrumental size. A multi-pass time-of-flight mass spectrometer has been developed to realize high mass resolution while avoiding an increase in instrumental size (see M. Toyoda, D. Okumura, M. Ishihara and I. Katakuse, J. Mass Spectrom., 2003, 38, pp. 1125-1142.). This instrument uses four toroidal electric fields each consisting of a combination of a cylindrical electric field and a Matsuda plate. The total flight time T can be lengthened by accomplishing multiple turns in an 8-shaped circulating orbit. In this apparatus, the spatial and temporal spread at the detection surface has been successfully converged up to the first-order term using the initial position, initial angle, and initial kinetic energy.
However, the TOFMS in which ions revolve many times in a closed trajectory suffers from the problem of overtaking. That is, because ions revolve multiple times in a closed trajectory, lighter ions moving at higher speeds overtake heavier ions moving at smaller speeds. Consequently, the fundamental concept of TOFMS that ions arrive at the detection surface in turn first from the lightest one does not hold.
The spiral-trajectory TOFMS has been devised to solve this problem. The spiral-trajectory TOFMS is characterized in that the starting and ending points of a closed trajectory are shifted from the closed trajectory plane in the vertical direction. To achieve this, in one method, ions are made to impinge obliquely from the beginning (see JP-A-2000-243345). In another method, the starting and ending points of the closed trajectory are shifted in the vertical direction using a deflector (see JP-A-2003-86129). In a further method, laminated toroidal electric fields are used (see JP-A-2006-12782).
Another TOFMS has been devised which is based on a similar concept but in which the trajectory of the multi-pass TOF-MS (see GB2080021) where overtaking occurs is zigzagged (see WO2005/001878).
One type of ion source for TOFMS is to ionize a sample by matrix-assisted laser desorption/ionization mass spectrometry (MALDIMS). Mass spectrometry in which MALDI and TOFMS are combined is referred to as MALDI-TOFMS. In a MALDI method, a sample is mixed and dissolved in a matrix of a liquid, crystalline compound, or a powdered metal showing an absorption band for the wavelength of the used laser light. The sample is solidified and irradiated with laser light to vaporize or ionize the sample. In a normal MALDI-TOFMS experiment, plural spots are prepared on a conductive sample plate. A mixture of the sample and the matrix is crystallized at each spot. Often, the sample plate is in the form of a microtiter plate. The user prepares a mixture solution of the sample and the matrix on the sample plate prior to a measurement. Recently, a method consisting of mixing the effluent from a separation means such as a liquid chromatograph with the matrix successively and dripping the mixture onto a sample plate has been used.
In a laser-assisted ionization process typified by MALDI, the initial energy distribution during ion generation is large. To converge the distribution in the direction of flight axis, delayed extraction is used in most cases. In this method, a pulsed voltage is applied after a delay of hundreds of nsec since laser irradiation. The performance of the MALDI-TOFMS has been greatly improved by the adoption of delayed extraction.
However, the delayed ion extraction technique has the disadvantage that the position of the focal point differs slightly according to m/z value. Consequently, if the instrumental conditions are so set that the mass resolution is enhanced at some m/z value, the mass resolution will get worse as it goes away from that m/z value. In order to obtain a high-quality mass spectrum, it is necessary to vary the instrumental conditions using the measured range or an m/z value of interest. Under existing conditions, a work for making adjustments to achieve optimum instrumental conditions based on user's experience is needed. Much labor is necessitated to make such adjustments.